Abstract [en]

Deep brain stimulation (DBS) is an effective surgical treatment for neurological diseases such as essential tremor, Parkinsonʹs disease (PD) and dystonia. DBS has so far been used in more than 70 000 patients with movement disorders, and is currently in trial for intractable Gilles de la Tourette’s syndrome, obsessive compulsive disorders, depression, and epilepsy. DBS electrodes are implanted with stereotactic neurosurgical techniques in the deep regions of the brain. Chronic electrical stimulation is delivered to the electrodes from battery-operated pulse generators that are implanted below the clavicle.

The clinical benefit of DBS is largely dependent on the spatial distribution of the electric field in relation to brain anatomy. To maximize therapeutic benefits while avoiding unwanted side-effects, knowledge of the distribution of the electric field in relation anatomy is essential. Due to difficulties in measuring electric fields in vivo, computerized analysis with finite element models have emerged as an alternative.

The aim of the thesis was to investigate technical and clinical aspects of DBS by means of finite element models, simulations, and visualizations of the electric field and tissue anatomy. More specifically the effects of dilated perivascular spaces filled with cerebrospinal fluid on the electrical field generated by DBS was evaluated. A method for patient-specific finite element modelling and simulation of DBS was developed and used to investigate the anatomical distribution of the electric field in relation to clinical effects and side effects. Patient-specific models were later used to investigate the electric field in relation to effects on speech and movement during DBS in patients with PD (n=10). Patient-specific models and simulations were also used to evaluate the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the electric field during DBS. In addition, methods were developed for visualization of atlas-based and patient-specific anatomy in 3D for interpretation of anatomy, visualization of neural activation with the activating function, and visualization of tissue micro structure. 3D visualization of anatomy was used to assess electrode contact locations in relation to stimulation-induced side-effects (n=331) during DBS for patients with essential tremor (n=28). The modelling, simulation, and visualization of DBS provided detailed information about the distribution of the electric field and its connection to clinical effects and side-effects of stimulation. In conclusion, the results of this thesis provided insights that may help to improve DBS as a treatment for movement disorders as well as for other neurological diseases in the future.

Abstract [en]

Deep brain stimulation (DBS) is an established treatment for Parkinsons disease. Success of DBS is highly dependent on electrode location and electrical parameter settings. The aim of this study was to develop a general method for setting up patient-specific 3D computer models of DBS, based on magnetic resonance images, and to demonstrate the use of such models for assessing the position of the electrode contacts and the distribution of the electric field in relation to individual patient anatomy. A software tool was developed for creating finite element DBS-models. The electric field generated by DBS was simulated in one patient and the result was visualized with isolevels and glyphs. The result was evaluated and it corresponded well with reported effects and side effects of stimulation. It was demonstrated that patient-specific finite element models and simulations of DBS can be useful for increasing the understanding of the clinical outcome of DBS.

Abstract [en]

Background/Aims: Deep brain stimulation (DBS) is widely used to treat motor symptoms in patients with advanced Parkinson’s disease. The aim of this study was to investigate the anatomical aspects of the electric field in relation to effects on speech and movement during DBS in the subthalamic nucleus. Methods: Patient-specific finite element models of DBS were developed for simulation of the electric field in 10 patients. In each patient, speech intelligibility and movement were assessed during 2 electrical settings, i.e. 4 V (high) and 2 V (low). The electric field was simulated for each electrical setting. Results: Movement was improved in all patients for both high and low electrical settings. In general, high-amplitude stimulation was more consistent in improving the motor scores than low-amplitude stimulation. In 6 cases, speech intelligibility was impaired during high-amplitude electrical settings. Stimulation of part of the fasciculus cerebellothalamicus from electrodes positioned medial and/or posterior to the center of the subthalamic nucleus was recognized as a possible cause of the stimulation-induced dysarthria. Conclusion: Special attention to stimulation-induced speech impairments should be taken in cases when active electrodes are positioned medial and/or posterior to the center of the subthalamic nucleus.

Abstract [en]

The aim was to quantify the influence of heterogeneous isotropic and heterogeneous anisotropic tissue on the spatial distribution of the electric field during deep brain stimulation (DBS). Three finite element tissue models were created of one patient treated with DBS. Tissue conductivity was modelled as I) homogeneous isotropic, II) heterogeneous isotropic based on MRI, and III) heterogeneous anisotropic based on diffusion tensor MRI. Modelled DBS electrodes were positioned in the subthalamic area, the pallidum, and the internal capsule in each tissue model. Electric fields generated during DBS were simulated for each model and target-combination and visualized in 3D with isolevels at 0.20 (inner), and 0.05 V m-1 (outer). F-test and vector analysis was used for statistical evaluation of the distribution of the electric field. Heterogeneous isotropic tissue altered the spatial distribution of the electric field by up to 4% at inner, and up to 10% at outer isolevel. Heterogeneous anisotropic tissue had a larger impact on the distribution of the electric field with an influence of up to 18% and 15% at each isolevel, respectively. The influence of heterogeneous and anisotropic tissue on the electric field may be clinically relevant in anatomic regions that are functionally subdivided and surrounded by multiple fibres of passage.

Abstract [en]

Objective: The posterior subthalamic area (PSA) is an emerging but relatively unexplored target for DBS treatment of tremor. The aim of the study was to explore the area further by evaluating the spatial distribution and the characteristics of stimulation-induced side effects in this area. Methods: Twenty-eight patients with essential tremor (ET) implanted with 33 DBS electrodes were evaluated concerning stimulation-induced side effects by testing each contact separately one year after surgery. The location of the side effects were plotted on axial slides of the Morel Stereotactic Atlas and a 3-dimensional model of the area for visualization was created. Results: Visualization of the contacts eliciting stimulation-induced side effects demonstrated that identical responses can be elicited from various points in the PSA and its vicinity. The majority of contacts inducing muscular affection and cerebellar symptoms, including dysarthria, could not be attributed to an effect on the internal capsule. Paresthesias, affecting various body parts were elicited throughout the area without a clear somatotopic pattern. Conclusion: Stimulation-induced side effects in the PSA and its vicinity are difficult to attribute to certain anatomical areas as the same response can be induced from various locations, and are thus of limited localizing value.